Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers

Azad Rahimpour, Hui Fern Koay, Anselm Enders, Rhiannon Clanchy, Sidonia B G Eckle, Bronwyn Meehan, Zhenjun Chen, Belinda Whittle, Ligong Liu, David P Fairlie, Chris C Goodnow, James McCluskey, Jamie Rossjohn, Adam P Uldrich, Daniel G Pellicci, Dale I Godfrey

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Abstract

Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-gamma, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor gammat (RORgammat), whereas RORgammat(lo) MAIT cells predominantly express T-bet and produce IFN-gamma. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Valpha19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.
Original languageEnglish
Pages (from-to)1095 - 1108
Number of pages14
JournalJournal of Experimental Medicine
Volume212
Issue number7
DOIs
Publication statusPublished - 2015

Cite this

Rahimpour, A., Koay, H. F., Enders, A., Clanchy, R., Eckle, S. B. G., Meehan, B., ... Godfrey, D. I. (2015). Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. Journal of Experimental Medicine, 212(7), 1095 - 1108. https://doi.org/10.1084/jem.20142110
Rahimpour, Azad ; Koay, Hui Fern ; Enders, Anselm ; Clanchy, Rhiannon ; Eckle, Sidonia B G ; Meehan, Bronwyn ; Chen, Zhenjun ; Whittle, Belinda ; Liu, Ligong ; Fairlie, David P ; Goodnow, Chris C ; McCluskey, James ; Rossjohn, Jamie ; Uldrich, Adam P ; Pellicci, Daniel G ; Godfrey, Dale I. / Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. In: Journal of Experimental Medicine. 2015 ; Vol. 212, No. 7. pp. 1095 - 1108.
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title = "Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers",
abstract = "Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-gamma, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor gammat (RORgammat), whereas RORgammat(lo) MAIT cells predominantly express T-bet and produce IFN-gamma. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Valpha19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.",
author = "Azad Rahimpour and Koay, {Hui Fern} and Anselm Enders and Rhiannon Clanchy and Eckle, {Sidonia B G} and Bronwyn Meehan and Zhenjun Chen and Belinda Whittle and Ligong Liu and Fairlie, {David P} and Goodnow, {Chris C} and James McCluskey and Jamie Rossjohn and Uldrich, {Adam P} and Pellicci, {Daniel G} and Godfrey, {Dale I}",
year = "2015",
doi = "10.1084/jem.20142110",
language = "English",
volume = "212",
pages = "1095 -- 1108",
journal = "Journal of Experimental Medicine",
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Rahimpour, A, Koay, HF, Enders, A, Clanchy, R, Eckle, SBG, Meehan, B, Chen, Z, Whittle, B, Liu, L, Fairlie, DP, Goodnow, CC, McCluskey, J, Rossjohn, J, Uldrich, AP, Pellicci, DG & Godfrey, DI 2015, 'Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers', Journal of Experimental Medicine, vol. 212, no. 7, pp. 1095 - 1108. https://doi.org/10.1084/jem.20142110

Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. / Rahimpour, Azad; Koay, Hui Fern; Enders, Anselm; Clanchy, Rhiannon; Eckle, Sidonia B G; Meehan, Bronwyn; Chen, Zhenjun; Whittle, Belinda; Liu, Ligong; Fairlie, David P; Goodnow, Chris C; McCluskey, James; Rossjohn, Jamie; Uldrich, Adam P; Pellicci, Daniel G; Godfrey, Dale I.

In: Journal of Experimental Medicine, Vol. 212, No. 7, 2015, p. 1095 - 1108.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers

AU - Rahimpour, Azad

AU - Koay, Hui Fern

AU - Enders, Anselm

AU - Clanchy, Rhiannon

AU - Eckle, Sidonia B G

AU - Meehan, Bronwyn

AU - Chen, Zhenjun

AU - Whittle, Belinda

AU - Liu, Ligong

AU - Fairlie, David P

AU - Goodnow, Chris C

AU - McCluskey, James

AU - Rossjohn, Jamie

AU - Uldrich, Adam P

AU - Pellicci, Daniel G

AU - Godfrey, Dale I

PY - 2015

Y1 - 2015

N2 - Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-gamma, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor gammat (RORgammat), whereas RORgammat(lo) MAIT cells predominantly express T-bet and produce IFN-gamma. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Valpha19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.

AB - Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-gamma, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor gammat (RORgammat), whereas RORgammat(lo) MAIT cells predominantly express T-bet and produce IFN-gamma. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Valpha19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.

UR - http://jem.rupress.org/content/212/7/1095.full.pdf+html

U2 - 10.1084/jem.20142110

DO - 10.1084/jem.20142110

M3 - Article

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SP - 1095

EP - 1108

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

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